HWN Suggests

Peripherally acting μ-opioid receptor antagonists as treatment options for constipation in noncancer pain patients on chronic opioid therapy

Opioid-induced constipation (OIC), a prevalent and distressing side effect of opioid therapy, does not reliably respond to treatment with conventional laxatives. OIC can be a treatment-limiting adverse event. Recent advances in medications with peripherally acting μ-opioid receptor antagonists, such as methylnaltrexone, naloxegol, and alvimopan, hold promise for treating OIC and thus extending the benefits of opioid analgesia to more chronic pain patients. Peripherally acting μ-opioid receptor antagonists have been clinically tested to improve bowel symptoms without compromise to pain relief, although there are associated side effects, including abdominal pain. Other treatment options include…

read full article

Featured

 Mu-Opioid Antagonists for the Treatment of Opioid-Induced Bowel Dysfunction

The systematic review found that oral naldemedine improves opioid-induced bowel dysfunction over two weeks in patients with cancer, and subcutaneous methylnaltrexone improves opioid-induced bowel dysfunction over two weeks in patients receiving palliative care. We have assigned a color recommendation of green (benefits greater than harms) for the use of oral naldemedine and subcutaneous methylnaltrexone in these patients.

Articles of Interest

PAMORAs in Opioid-Induced Constipation: Are We Following the Guidelines?

PAMORAs are underutilized in patients with OIC. GI prescribers offer PAMORAs at a higher proportion than other departments, and being seen in GI independently increases the likelihood of a patient receiving a PAMORA. This suggests that underutilization may be due to a lack of awareness and further education about PAMORAs is warranted.

Toxicity Is a Risk of PAMORA Interactions

Constipation is a bothersome, common, and underrecognized adverse effect (AE) of long-term opioid therapy. PAMORAs offer treatment for this condition and can improve patient adherence to the prescribed opioid therapy. However, it is crucial to understand the pharmacokinetic differences between the PAMORAs to aid in AE monitoring and minimize potentially strong drug-drug interactions (DDIs).

Are peripheral opioid antagonists the solution to opioid side effects?

Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role.

Development of Peripheral Opioid Antagonists: New Insights Into Opioid Effects

These peripherally acting μ-opioid receptor antagonists selectively reverse opioid actions mediated by receptors outside the central nervous system, while preserving centrally mediated analgesia. Methylnaltrexone, administered subcutaneously, has been approved in the United States, Europe, and Canada. In the United States, it is indicated for the treatment of opioid-induced constipation in patients with advanced illness (eg, cancer, AIDS) who are receiving palliative care, when response to laxative therapy has not been sufficient.

Efficacy and Safety of Peripherally Acting μOpioid Receptor Antagonist (PAMORAs) for the Management of Patients With Opioid-Induced Constipation: A Systematic Review

In treating chronic and acute pain, opioids are widely used. Although they do provide analgesia, their usage does come with adverse events (AEs). One of the most burdensome is opioid-induced bowel dysfunction, and more specifically opioid-induced constipation (OIC). The pathogenesis of these AEs is well known as the consequence of the action of opioids on m-receptors in the enteric nervous system. In recent years, medicines counteracting this specific action at the receptors have been registered for clinical use: the peripherally acting μ-opioid receptor antagonists (PAMORAs). The knowledge of their comparative efficacy and tolerability is very important for physicians and patients in opioid therapy. This systematic review of the existing literature on PAMORAs aimed to study the relative clinical advantages and disadvantages.

Insights into the Current and Possible Future Use of Opioid Antagonists in Relation to Opioid-Induced Constipation and Dysbiosis

When non-opioid therapies fail to overcome the OIC, opioid antagonists with peripheral, fast first-pass metabolism, and gastrointestinal localized effects remain the drug of choice for OIC...

Methylnaltrexone (Relistor) for Opioid-Induced Constipation

Methylnaltrexone (Relistor) is labeled for the treatment of opioid-induced constipation in patients with advanced illness who have not responded to laxative therapies. As a selective antagonist of peripheral mu-opioid receptors, methylnaltrexone inhibits opioidinduced gastrointestinal (GI) hypomotility without central nervous system effects such as sedation or change in mental status.

Methylnaltrexone in the treatment of opioid-induced constipation

Methylnaltrexone is a peripherally restricted, μ opioid receptor antagonist that accelerates oral–cecal transit in patients with opioid-induced constipation without reversing the analgesic effects of morphine or inducing symptoms of opioid withdrawal.

Novel opioid antagonists for opioid-induced bowel dysfunction and postoperative ileus

The peripherally acting μ-receptor antagonists methylnaltrexone and alvimopan are a new class of drugs designed to reverse opioid-induced side-effects on the gastrointestinal tract without compromising pain relief.

Opioid Induced Constipation – Part 2: Newer Therapies

Traditional oral and rectal laxatives have been the mainstay of treatment in OIC for many years. However, novel approaches to treat OIC show promise. Of the pharmacologic interventions described above, methylnaltrexone has been the best studied. It is reasonable to give methylnaltrexone after failure of oral laxatives

Peripherally Acting Opioid Antagonists in the Treatment of Opiate-Related Constipation: A Systematic Review

Many patients treated with opioids suffer from constipation. Opiate- or opioid-related constipation is not only a frequent but also a distressing symptom and difficult to treat. There is emerging evidence regarding a novel approach to the management of opiate-related constipation. The aim of this paper is to collect, critically appraise, and summarize the evidence on the effectiveness of recently developed peripherally acting μ-receptor antagonists in the treatment of opiate-related constipation.

Peripherally Acting μ-Opioid Receptor Antagonists for the Treatment of Opioid-Related Side Effects: Mechanism of Action and Clinical Implications

Optimal use of opioids for analgesia is often compromised by OIC, which is mediated primarily by µ-opioid receptors in the GI tract. OIC exacts a considerable burden on patients in terms of impaired QOL and activities of daily living. Early attempts to treat OIC with naloxone led to the development of PAMORAs. Three currently approved PAMORAs have shown efficacy in treating OIC in patients with chronic pain, and new PAMORAs currently in development are likely to provide more treatment options in this patient population.

The Use of Peripheral μ-Opioid Receptor Antagonists (PAMORA) in the Management of Opioid-Induced Constipation: An Update on Their Efficacy and Safety

Peripherally acting μ-opioid receptor antagonists (PAMORAs) constitute a class of drugs which reverse opioid-induced constipation (OIC) with similar opioid analgesic effects. OIC differs from other forms of constipation in that it is an iatrogenic condition that occurs when an opioid acts on the dense network of μ-opioid receptors in the enteric system, which affect a variety of functions including gastrointestinal motility, secretion, and other factors that can cause bowel dysfunction.

Resources

Movantik (Naloxegol)

If you’re taking opioids and are constipated, don’t suffer in silence.

Relistor (Methylnaltrexone)

Relistor is specifically designed to target the constipating effect opioids have in the gut.

Symproic (Naldemedine)

SYMPROIC is a prescription medicine used to treat constipation that is caused by prescription pain medicines called opioids, in adults with long-lasting (chronic) pain that is not caused by active cancer.